Catheter system for acute neuromodulation

ABSTRACT

A neuromodulation system includes a first therapy element adapted for positioning within a superior vena cava, and a second therapy element adapted for positioning within a pulmonary artery. Each therapy element is carried on a corresponding elongate flexible shaft. One of the shafts is slidably received within a lumen of the other so that the second therapy element may be advanced within the body relative to the first. A stimulator energizes the first therapy element within the first blood vessel to deliver therapy to a first nerve fiber disposed external to the superior vena cava and to energize the second therapy element within the pulmonary artery to deliver sympathetic therapy to a second nerve fiber disposed external to the pulmonary artery. For treatment of heart failure, the first nerve fiber may be a vagus nerve and the second nerve fiber may be a sympathetic nerve fiber.

PRIORITY

This application claims the benefit of U.S. Provisional Application No.61/506,164, filed 11 Jul. 2011, which is incorporated herein byreference.

TECHNICAL FIELD OF THE INVENTION

The present application generally relates to systems and methods foracute neuromodulation using stimulation elements disposed within thevasculature.

BACKGROUND

Acute heart failure syndromes (AHFS) are serious conditions resulting inmillions of hospitalizations each year. AHFS treatments can includepharmacologic inotrope administration—however side effects of suchtreatments, including arrhythmias and increased myocardial oxygendemand, can contribute to patient mortality. Additional treatmentsinclude administration of diuretics to treat pulmonary edema resultingfrom AHFS.

The autonomic nervous system includes the parasympathetic nervous systemand the sympathetic nervous system. The parasympathetic and sympatheticnervous system have somewhat opposing effects on the cardiovascularsystem. One function of the parasympathetic nervous system is to slowthe heart through action of the vagus nerve. On the other hand, thesympathetic nervous system is associated with increasing the heart rateand increasing the contractility of the heart. The disclosed system andmethod may be used to augment balance between the sympathetic andparasympathetic systems in AHFS patents so as to lower heart rate,elevate heart rate and/or increase heart contractility.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1-4 are a sequence of drawings illustrating deployment of a firstembodiment of a catheter system, in which:

FIG. 1 shows the system in a blood vessel prior to expansion of theanchoring element;

FIG. 2 is similar to FIG. 1 but shows the anchoring element expanded;

FIG. 3 illustrates the system following removal of the guide wire anddilator, and

FIG. 4 is similar to FIG. 3 but shows a Swan-Ganz catheter extendingthrough the lumen of the catheter.

FIG. 5A is similar to FIGS. 4 but shows a second neuromodulation deviceextending through the lumen of the catheter.

FIG. 5B schematically illustrates positioning of the neuromodulationdevice of FIG. 5A within the vasculature;

FIGS. 6 and 7 are similar to FIGS. 1 and 4 but show a second alternativeconfiguration for expanding the anchoring element.

DETAILED DESCRIPTION

The present application discloses a catheter system for neuromodulation.One application of the system is for acute use in treating AHFS throughparasympathetic and/or sympathetic neuromodulation. However it should beunderstood that the system may alternatively be used to treat otherconditions, or to maintain autonomic balance at times where thepatient's own nervous system could benefit from assistance inmaintaining autonomic balance. One example of this latter application isto use the system to maintain autonomic balance while the patient isintubated, is in a coma, or is otherwise experiencing autonomicdysfunction. Other conditions that could be treated with acuteneuromodulation include, but are not limited to, acute myocardialinfarction, pulmonary embolism, hemorrhage, systemic inflammatoryresponse syndrome (SIRS), sepsis, and post-surgery autonomicdysfunction.

A neuromodulation system for treating AHFS provides therapeutic elementsfor modulation of parasympathetic and/or sympathetic fibers. In someembodiment, only parasympathetic fibers are stimulated, while in otherembodiments parasympathetic and sympathetic fibers are stimulated at thesame time and/or at different times to improve autonomic balance in theheart. In preferred embodiments, the therapeutic elements are positionedon one or more catheters positioned in the vasculature of the patientand are energized to modulate nerve fibers positioned outside thevascular walls. Modulation may be carried out to activate and/or inhibitor block activation of target nerve fibers. In the disclosed system, thetherapeutic elements are described as electrodes, although it iscontemplated that other forms of therapeutic elements (including, butnot limited to, ultrasound, thermal, or optical elements) may instead beused.

The parasympathetic and sympathetic fibers may be modulated from thesame therapeutic element or element array, or from different elements orelement arrays. Elements used to modulate sympathetic fibers may bepositioned in the same blood vessels as those used for theparasympathetic fibers, or they may be in different blood vessels. Theblood vessel and the target position of the therapeutic elements withina chosen vessel is selected based on the vessel's anatomic locationrelative to the target fiber so as to position the therapeutic elementin close proximity to the target fiber while minimize collateraleffects. For example, in the canine model, right sympathetic fibersmodulating left ventricular contractility converge at the commonpulmonary artery and course in the pulmonary artery nerves. Leftsympathetic fibers modulating ventricular contractility are found nearthe common pulmonary artery, pulmonary artery nerves, and ventrallateral cardiac nerve. In contrast, sympathetic fibers controllingchronotropic and dromotropic functions are found between the superiorvena cava (SVC) and aorta, between the common pulmonary artery and theproximal right pulmonary artery, between the left superior pulmonaryvein and the right pulmonary artery, and elsewhere. J. L. Ardell et al,Differential sympathetic regulation of automatic, conductile, andcontractile tissue in dog heart. The anatomy thus allows a therapeuticelement to be positioned to selectively stimulate sympathetic fiberscontrolling ventricular inotropy to increase contractility, whileavoiding chronotropic/dromotropic effects so as not to triggertachycardia.

In human use, modulation of sympathetic fibers may be achieved using atherapeutic element positioned within the pulmonary artery so as tostimulate sympathetic fibers to increase inotropy. Moreover, therapeuticelements could additionally or alternatively be employed to stimulateparasympathetic fibers that lower heart rate. Such fibers may also beactivated using intravascular electrodes located in the pulmonaryarteries, although in other embodiments vagal or other parasympatheticfibers are modulated using a therapeutic element in the superior venacava or the internal jugular vein, preferably on the right side.

In some embodiments, combined or alternating modulation of theparasympathetic and sympathetic fibers may be employed to optimize theopposing effects of parasympathetic and sympathetic modulation on heartrate—such that modulation optimizes the ability of the sympatheticsystem to drive the heart rate and the parasympathetic system to “applythe brakes” to slow the heart when necessary. Sensed or derivedhemodynamic parameters may be used by the system to select and implementstimulation parameters, algorithms and/or to identify the therapeuticelement(s) to be activated at a given time. Suitable sensed or derivedhemodynamic parameters include pulmonary capillary wedge pressure(PCWP), cardiac index, derivations of vascular resistance, heart rate,and blood pressure (arterial). Other parameters may include centralvenous pressure, CO/CI, and cardiac filling pressures.

FIGS. 1-4 illustrate a first embodiment of a catheter system 10, whichincludes a treatment catheter 12, a dilator 14, and a guide wire 16. Thetreatment catheter 12 includes a tubular inner sheath 30 and a tubularouter sheath 32, which are connected at their distal end sections.

The distal end section of the outer sheath includes one or moreanchoring elements 18 that are expanded or extended into contact withthe surrounding vessel wall so as to anchor the catheter in a desiredlocation. The anchoring element(s) may be an expandable basket orstent-like device, or one or more spline elements as illustrated in thedrawings. In the illustrated configuration, these elements are outwardlyexpandable into contact with the vessel wall W when the outer sheath 32is pushed distally relative to the inner sheath 30 as illustrated inFIG. 2. Since the inner and outer sheaths are connected at their distalend portions, sliding the outer sheath distally relative to the innersheath causes the anchoring elements to bow outwardly into contact withthe vessel wall as shown. Stimulation electrodes 20 are mounted to orformed on the anchoring element(s) 18, or the anchoring element(s) maythemselves be configured to function as electrodes. The electrodes arepreferably positioned such that expanding the anchoring elements intocontact with the vessel wall places the active surfaces of theelectrodes into contact with the vessel wall, allowing energy forneuromodulation to conduct from the electrodes through the vessel wallto target nerve fibers adjacent to the vessel (e.g. in the adjacentextravascular space).

The inner sheath 30 includes a lumen, allowing the catheter 12 tofunction both as a neuromodulation catheter and an introducer for othermedical devices useful for the procedure. Examples include catheters forpatient monitoring (e.g. Swan-Ganz), additional electrode catheters orleads for a variety of applications such as mapping target stimulationsites, cardiac pacing, or ablation, or catheters/leads carryingneuromodulation electrodes positionable at a second intravascular siteto target additional nerve fibers.

In one method of using the first embodiment, a percutaneous Seldingertechnique is used to place the guidewire 16 into the venous vasculature,such as via the femoral vein, internal or external jugular vein, orsubclavian vein. The dilator 14, which is preferably preloaded into thelumen of the inner sheath 30, is advanced together with the catheterover the wire and directed to the target blood vessel. The user advancesthe outer sheath 32 relative to the inner sheath 30 (such as by holdingthe hub of the inner sheath while pushing the hub of the outer sheathdistally as shown in FIG. 2)—causing the anchoring elements 18 to expandinto contact with the surrounding vessel wall, thus anchoring thecatheter at the target site in the vessel and placing the electrodes 20into contact with the vessel wall. The relative positions of the innerand outer sheath hubs may be locked using a ratchet or locking mechanism(not shown) to maintain the anchoring elements in the expanded position.

The dilator and wire are removed from the catheter lumen either beforeor after anchoring of the catheter.

In one embodiment, the target vessel is the superior vena cava, and thecatheter 12 is anchored such that energizing the electrodes (or a selectgroup of electrodes within the array) will cause a desired effect (e.g.enhance, augment, inhibit or block signaling) on vagus nerve fibersadjacent to the superior vena cava. Once the electrodes are expandedinto contact with the vessel wall, mapping procedures may be carried outas known in the art (measuring the effect of stimulus at variouselectrode locations) to identify the optimal positions of the electrodesor to identify the best combination of electrodes within the array toenergize for the desired response.

Additional medical devices are advanced through the inner sheath lumenas discussed above, such that their distal portions extend from thedistal end of the catheter. FIG. 4 shows use of a Swan-Ganz catheter 22through the inner sheath 30. FIG. 5A shows that a second electrode leador catheter 24 can be advanced through the lumen of the inner sheath 30.The second electrode lead or catheter may have one or more expandableanchoring elements 26 as discussed above with respect to the catheter 12(and as shown in FIG. 5A in the unexpanded position), with electrodes 34mounted to or formed on the anchoring elements 26 as disclosed. Thesecond electrode lead or catheter 24 may include an inflatable balloon28 on its distal tip as shown, to facilitate advancement of the secondelectrode lead/catheter 24 to a target site. It may also include sensingfunctionality, such as the ability to sense pressures including, but notlimited to, PCWP. For example, if the second electrode lead/catheter 24is to be positioned within the pulmonary artery, inflating the balloonwithin the right ventricle can help the electrode lead/catheter floatwith the flowing blood into the pulmonary artery in the manner similarto the way in which a Swan-Ganz catheter is positioned. The balloon 28may be positioned on the second lead/catheter 34 itself, or on anadditional catheter extending through a lumen in the lead/catheter 34.

In one exemplary procedure using the FIG. 5A embodiment, the electrodes20 of the catheter 12 are anchored in the superior vena cava asdiscussed above for neuromodulating parasympathetic activity of thevagus nerve (to slow the heart, for example), and the electrodes 34 ofthe second lead/catheter 24 are anchored in the pulmonary artery fordirecting energy to sympathetic nerves that will enhance heartcontractility and/or increase heart rate. Referring to FIG. 5B, in apositioning method according to this embodiment, the catheter isadvanced into the superior vena cava and anchoring elements 18 areexpanded to position the electrodes 20 against the wall of the SVC,placing the first electrode array 40 in position to stimulate the vagusnerve. Next, the second lead/catheter 24 is further extended from thelumen of the inner sheath 30, and passed or caused to through the rightatrium and right ventricle of the heart and into the pulmonary arteryusing the method described in the prior paragraph or alternativemethods. Once in a target position within the pulmonary artery (e.g.pulmonary trunk, or left or right pulmonary artery), the anchoringelements of the second lead/catheter 24 are expanded, positioning theelectrodes 34 in apposition with the pulmonary artery wall and thusplacing the second electrode array 42 in position to stimulatesympathetic nerves (or, if desired, parasympathetic nerves) in proximityto the pulmonary artery. Pressure may be monitored using pressuretransducers on the second lead/catheter, and/or the balloon may be usedto monitor pulmonary capillary wedge pressure.

In a slightly modified version of the FIG. 1-4 embodiment, deployment ofthe anchoring elements 18 is accomplished by pulling the inner sheath 30proximally relative to the outer sheath 32. FIGS. 6-7 show yet anotherconfiguration utilizing anchoring elements that are self-expandable uponretraction of an outer sleeve 36 (shown compressing the anchoringelements in FIG. 6 and withdrawn from them in FIG. 7) that maintains theanchoring element(s) in a compressed position until it is retracted. Instill other embodiment, pull cables may be tensioned from the proximalend of the catheter to expand the anchoring elements.

The disclosed catheter system may be coupled to external pulse generatorused to energize the electrodes using stimulation parameters selected tocapture the target nerve fibers and to achieve the desiredneuromodulation. Feedback to the pulse generator is provided by one ormore diagnostic sensors, including feedback from sensors mounted on orextending through the lumen of the catheter-introducer. The simulationparameters may be determined or adjusted in response to informationsensed by the sensors and/or derived from sensor feedback. Suitablesensed or derived hemodynamic parameters include pulmonary capillarywedge pressure (PCWP), cardiac index, derivations of vascularresistance, heart rate, blood pressure (arterial). Other parameters mayinclude central venous pressure, CO/CI, and cardiac filling pressures.

We claim:
 1. A method of treating a patient, comprising: (a) stimulatingat least one parasympathetic nerve fiber using a first therapeuticelement disposed in a superior vena cava of the patient; and (b)stimulating at least one sympathetic nerve fiber using a secondtherapeutic element disposed in a pulmonary artery of the patient. 2.The method of claim 1, further including: introducing a therapy systeminto the vasculature, the therapy system including the first therapeuticelement and the second therapeutic element coupled to the firsttherapeutic element, advancing the therapy device within the vasculatureto position the first therapeutic element within the superior vena cava;and advancing the second therapeutic element relative to the firsttherapeutic element to position the second therapeutic element withinthe pulmonary artery.
 3. The method of claim 1, wherein the firsttherapeutic element is provided on a first elongate shaft, the secondtherapeutic element is provided on a second elongate shaft, and whereinadvancing the second therapeutic element relative to the firsttherapeutic element includes sliding a first one of the first and secondshafts within a lumen of a second one of the first and second shafts. 4.The method of claim 3, wherein advancing the second therapeutic elementincludes, with the second therapeutic element disposed in the heart,inflating a balloon carried by the second therapeutic element such thatthe balloon and second therapeutic element are carried by blood flowinto the pulmonary artery.
 5. The method of claim 1, wherein the firsttherapeutic element comprises electrodes, and wherein step (a) includesenergizing the electrodes.
 6. The method of claim 5, further includinganchoring the first therapeutic element within the superior vena cava tobias the electrodes into contact with a wall of the superior vena cava.7. The method of claim 1, wherein the second therapeutic elementcomprises electrodes, and wherein step (b) includes energizing theelectrodes.
 8. The method of claim 7, further including anchoring thesecond therapeutic element within the pulmonary artery to bias theelectrodes into contact with a wall of the pulmonary artery.
 9. Themethod of claim 1, further including sensing at least one parameterwithin the body using the therapy device.
 10. The method of claim 9,wherein the sensed parameter comprises pressure.
 11. A neuromodulationsystem for treating a patient, comprising: a first therapy elementadapted for positioning within a first blood vessel, the first therapyelement carried on a first elongate shaft; a second therapy elementadapted for positioning with a second blood vessel different from thefirst blood vessel, the second therapy element carried on a secondshaft, wherein one of the first and second shafts is slidably receivedwithin a lumen of the other of the first and second shafts; and astimulator configured to (a) energize the first therapy element withinthe first blood vessel to deliver therapy to a first nerve fiberdisposed external to the first blood vessel and (b) energize the secondtherapy element within the second blood vessel to deliver sympathetictherapy to a second nerve fiber disposed external to the first bloodvessel.
 12. The system of claim 11, further including control means forcontrolling the stimulation in response to sensed heart rate and/orblood pressure of the patient.
 13. The system of claim 11, wherein eachof the first and second therapy elements is at least partiallyexpandable to position the first and second therapy elements in contactwith surrounding walls of the first and second blood vessels.
 14. Thesystem of claim 11, wherein the second therapy element is adapted forpositioning within a pulmonary artery.
 15. The system of claim 14,further including an expandable balloon coupled to the second therapyelement, the balloon positioned such that when the first therapy elementis retained in the first blood vessel, expansion of the balloon causesthe second therapy element to be carried by blood flow from the heart tothe pulmonary artery.
 16. The system of claim 14, wherein the firsttherapy element is adapted for positioning within a superior vena cava.